Efficacy and safety of a 4-year combination therapy of growth hormone and gonadotropin-releasing hormone analogue in pubertal girls with short predicted adult height.

Dotremont, Hilde; France, Annick; Heinrichs, Claudine; Tenoutasse, Sylvie; Brachet, Cécile; Cools, Martine; De Waele, Kathleen; Massa, Guy; Lebrethon, Marie-Christine; Gies, Inge; Van Besien, Jesse; Derycke, Christine; Ziraldo, Mathieu; De Schepper, Jean; Beauloye, Véronique; Verhulst, Stijn; Rooman, Raoul; den Brinker, Marieke

doi:10.3389/fendo.2023.1113750

Article (Scientific journals)

Efficacy and safety of a 4-year combination therapy of growth hormone and gonadotropin-releasing hormone analogue in pubertal girls with short predicted adult height.

Dotremont, Hilde; France, Annick; Heinrichs, Claudine et al.

2023 • In Frontiers in Endocrinology, 14, p. 1113750

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/313291

DOI
10.3389/fendo.2023.1113750

PubMed
37008942

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Keywords :

adult height; girls; gonadotropin-releasing hormone agonist (GnRHa); growth hormone treatment (GH); puberty; short stature children; Growth Hormone; Gonadotropin-Releasing Hormone; Human Growth Hormone; Female; Humans; Adult; Child; Case-Control Studies; Body Height; Human Growth Hormone/therapeutic use; Puberty, Precocious/drug therapy; Endocrinology, Diabetes and Metabolism

Abstract :

[en] [en] OBJECTIVES: To improve adult height in pubertal girls with a poor height prediction, treatment with growth hormone (GH) can be used in combination with a gonadotropin releasing hormone agonist (GnRHa), to delay closure of the growth plates. However, there are few studies to support this practice, and they show conflicting results. The objective of this trial is to assess the safety and efficacy of this combination treatment in early pubertal girls with a short predicted height, in comparison with matched controls. DESIGN PATIENTS AND METHODS: We designed an open-label, multicenter, interventional case-control study. Early pubertal girls with predicted adult height (PAH) below -2.5 SDS, were recruited in tertiary care centers in Belgium. They were treated for four years with GH and GnRHa. The girls were followed until adult height (AH) was reached. AH vs PAH, AH vs Height at start, and AH vs Target Height (TH) were evaluated, as well as safety parameters. Control data were assembled from historical patient files or from patients who preferred not to participate in the study. RESULTS: Sixteen girls with mean age ( ± SD) at start of 11.0 years (± 1.3) completed the study protocol and follow-up. Their mean height ( ± SD) increased from 131.3 ± 4.1 cm (-2.3 ± 0.7 SDS) at start of treatment to 159.8 ± 4.7 cm (-1.1 ± 0.7 SDS) at AH. In matched controls, height increased from 132.3 ± 4.2 cm (-2.4 ± 0.5 SDS) to 153.2 ± 3.4 cm (-2.1 ± 0.6 SDS) (p<0.001). AH surpassed initial PAH by 12.0 ± 2.6 cm in treated girls; and by 4.2 ± 3.6 cm in the controls (p<0.001). Most treated girls reached normal adult height (>-2SD) (87.5%) and 68.7% reached or superseded the target height (TH), which was the case in only a minority of the controls (37.5% and 6.2%, respectively) (p= 0.003 and 0.001). A serious adverse event possibly related to the treatment, was a fracture of the metatarsals. CONCLUSION: A four-year GH/GnRHa treatment in early pubertal girls with a poor PAH seems safe and results in a clinically relevant and statistically significant increase in AH compared with matched historical controls. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT00840944.

Disciplines :

Endocrinology, metabolism & nutrition

Author, co-author :

Dotremont, Hilde; Department of Pediatrics, University Hospital Antwerp, Edegem, Belgium ; Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Edegem, Belgium

France, Annick; Department of Pediatrics, University Hospital Antwerp, Edegem, Belgium ; Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Edegem, Belgium

Heinrichs, Claudine; Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium

Tenoutasse, Sylvie; Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium

Brachet, Cécile; Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium

Cools, Martine; Department of Pediatric Endocrinology, Department of Internal Medicine and Pediatrics, Ghent University, Ghent University Hospital, Ghent, Belgium

De Waele, Kathleen; Department of Pediatric Endocrinology, Department of Internal Medicine and Pediatrics, Ghent University, Ghent University Hospital, Ghent, Belgium

Massa, Guy; Department of Pediatrics, Jessa Hospital, Hasselt, Belgium

Lebrethon, Marie-Christine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie

Gies, Inge; Department of Pediatric Endocrinology, University Hospital Brussels, Brussels, Belgium

More authors (8 more)

Language :

English

Title :

Efficacy and safety of a 4-year combination therapy of growth hormone and gonadotropin-releasing hormone analogue in pubertal girls with short predicted adult height.

Publication date :

2023

Journal title :

Frontiers in Endocrinology

eISSN :

1664-2392

Publisher :

Frontiers Media S.A., Switzerland

Volume :

Pages :

1113750

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.frontiersin.org/articles/10.3389/fendo.2023.1113750/full

Funding text :

This work was supported by the Belgian Society for Pediatric Endocrinology and Diabetes (BESPEED). Study medication was provided by Ferring. Ferring was not involved in the study design, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. AcknowledgmentsThis work was supported by the Belgian Society for Pediatric Endocrinology and Diabetes (BESPEED). Study medication was provided by Ferring. Ferring was not involved in the study design, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

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